Opioids,testosterone and suicide

Opioid use disorder and suicidal behaviour are major public health problems in many countries. Individuals who use opioids are much more likely than those who do not consume opioids to die by suicide (Oquendo and Volkow, 2018). Opioid use disorder is associated with a rise of 40% to 60% in the risk of suicidal ideation (Oquendo and Volkow, 2018). Individuals using opioids frequently twice as likely to attempt suicide as individuals who do not consume opioids (Oquendo and Volkow, 2018). In the United States, opioid use disorder is associated with more than doubled risk of suicide among females and elevated suicide risk among males by one-third (Oquendo and Volkow, 2018). Clinicians and researchers believe that some cases of death among opioid users regarded as accidental overdoses or ‘undetermined’ are in fact suicides (Oquendo and Volkow, 2018). It means that there may be more suicides among opioid users than reported. In this commentary, I propose that inhibition of testosterone production by opioids may contribute to the pathophysiology of suicidal behaviour among male opioid users.

The inhibitory impacts of opioid substances on the hypothalamic–pituitary–gonadal axis have been recognized for several decades (Duca et al., 2019). All opioids reduce testosterone production because they hamper secretion of hypothalamic gonadotropin-releasing hormone and disrupt its normal pulsatility (Duca et al., 2019). Opioid use decreases levels of testosterone in men regardless of the route of administration (Duca et al., 2019).

Testosterone deficiency leads to decreased libido and sexual activity, erectile dysfunction, hot flushes, fatigue, depressed mood, reduced memory and concentration, insomnia, decreased muscle strength, increased body fat and body mass index (Duca et al., 2019). Some studies suggest that lower testosterone levels may be associated with suicidal behaviour (Sher, 2018; Tripodianakis et al., 2007). Tripodianakis et al. (2007) compared testosterone levels in male psychiatric patients who made a suicide attempt and healthy male controls. The authors of the study found that suicide attempters had significantly lower testosterone levels in comparison with controls. Violent suicide attempters had lower testosterone levels compared to non-violent attempters.

The effect of testosterone on suicidal behaviour may be a result of direct testosterone effects on certain brain circuits (Sher, 2018). Goetz et al. (2014) performed a study that demonstrated that testosterone affects brain circuits. They observed that administration of testosterone rapidly elevated blood testosterone levels and was associated with increased reactivity of the amygdala, hypothalamus and periaqueductal grey to angry facial expressions. The authors concluded that testosterone quickly potentiates the reaction of neural circuits mediating threat processing and aggressive behaviour in men.

The impact of testosterone on suicidality may also be mediated by testosterone influences on mood and cognition. Multiple lines of evidence have demonstrated that mood and cognitive impairments play a role in the pathophysiology of suicidal behaviour (Sher, 2018).

It is reasonable to hypothesize that testosterone-reducing effects of opioids may contribute to suicidal behaviour among opioid users. Probably, blood testosterone levels should be examined in individuals taking opioids. Male opioid users who have low testosterone levels should be evaluated for suicidality. It is important to note that many factors including obesity, alcohol abuse, cigarette smoking, excessive caffeine intake and environmental pollution may reduce testosterone levels in men in Western countries (Duca et al., 2019).

Research studies are needed to find out whether testosterone supplementation may reduce suicidal behaviour among male opioid users. Testosterone supplementation may be an effective treatment intervention in men who use opioids and who are also at high risk of suicide. On a more general note, it is necessary to evaluate which are the best interventions to prevent suicide in opioid users. A connection between opioid use disorder and suicidality indicates that there may be advantages of coordination between opioid abuse prevention and suicide prevention efforts. Public health resources aimed to tackle both suicide and opioid use disorder need to be created and put into practice. A high-quality assessment of acute and chronic suicide risk along with prompt access to mental health treatment is of vital significance to reduce opioid-related deaths by suicide. Individuals with opioid use disorders need to be screened for suicide ideation, intent and plan regularly and continuously during treatment.